Our overall goal is to identify those cellular and tissue kinetic parameters which contribute significantly toward determining the response of normal and malignant tissues to fractionated regimes of x-irradiation and combined treatment with chemotherapy and radiotherapy. Initially, we will evaluate the cellular and tissue responses of two established lines of the C3H mouse mammary tumor (S102F and Slow) and two normal tissues, duodenum and bone marrow following single doses and fractionated protocols of x-irradiation as well as single doses of adriamycin and adriamycin plus x-irradiation. Such parameters as rates of DNA synthesis, rates of cell loss, cell-cycle transit times, the hypoxic cell fraction, reoxygenation rates etc. will be determined and correlated with such clinical responses as LD50/6 (gut death) LD50/30 (bone marrow death), tumor volumetric regression rates, growth delay, and tumor local control (TCD50/120). The kinetic parameters will be stimulated by a matrix-algebraic methodology and this model will be used to predict an "optimum" fractionated protocol for this murine-tumor model and the prediction will be evaluated experimentally as a "feed-back" approach to help us in understanding these complex phenomena in vivo. It is anticipated that the new insights obtained will have direct application for the improvement of human cancer therapy.